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Projekt Druckansicht

Detektion sekundärer neurodegenerativer Prozesse nach Subarachnoidalblutung mit dem PET-Tracer cis-4-[18F]fluoro-D-Prolin und funktioneller MRT sowie Untersuchung des neuroprotektiven Effekts einer frühzeitigen Therapie mit Argon im Modell der Ratte

Fachliche Zuordnung Anästhesiologie
Nuklearmedizin, Strahlentherapie, Strahlenbiologie
Förderung Förderung von 2018 bis 2025
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 412303240
 
Erstellungsjahr 2025

Zusammenfassung der Projektergebnisse

This project aimed to improve the understanding of subarachnoid hemorrhage (SAH) using animal models, with a particular focus on establishing imaging methods for detecting secondary neurodegenerative damage. Additionally, a rat model of traumatic brain injury (TBI) was used for longitudinal monitoring of secondary lesions by means of small animal imaging. Initially, the SAH model in rats was re-established and technically refined in Aachen. It became clear that both the surgical technique and the choice of rat strain were critical to success: switching from the supplier Janvier to Charles River significantly improved SAH induction, as anatomical differences in the cervical vessels significantly affected the model's reproducibility. An unexpected finding was the frequent occurrence of additional bleeding types (e.g., subdural hematomas) and ischemic lesions, which complicated data interpretation. However, this reflects the clinical reality, where SAH in humans rarely presents in isolation. Another major methodological challenge was the placement of intracranial pressure (ICP) and cerebral blood flow (CBF) probes, which themselves induced brain damage and led to strong signals in autoradiography using the tracer cisF18DPro. A modified surgical technique (i.e., more precise drilling with cooling) successfully reduced these artifacts. This refinement allowed for artifactfree tracer distribution and the detection of genuine neurodegenerative regions, including the hippocampus, striatum, and thalamus. A key finding was that cisF18DPro is more sensitive to early tissue damage than FDG. The study also revealed that even minor surgical interventions can induce substantial changes, which was evident even in SHAM animals. This emphasizes the importance of rigorous control groups and is an important consideration for preclinical modeling. In parallel, a TBI model using controlled cortical impact (CCI) was established at the Forschungszentrum Jülich. Here, too, cisF18DPro reliably detected secondary neurodegeneration, both ex vivo and in longitudinal PET/MRI studies. The combination of cisF18DPro-PET and T2-weighted MRI enabled a spatially and temporally detailed visualization of primary and secondary brain lesions. A correlation was observed between the extent of the primary lesion and the magnitude of secondary damage in the thalamus and hippocampus. In addition, changes in metabolite levels and water content in affected brain regions indicated progressive neurodegenerative processes, the analysis of which is still ongoing. This study provides significant contributions to the optimization of experimental models in SAH and TBI research. The tracer cisF18DPro proved particularly suitable for detecting subtle brain damage. The findings highlight the importance of technical precision, standardized models, and critical evaluation of experimental artifacts for both preclinical imaging and animal welfare.

Projektbezogene Publikationen (Auswahl)

 
 

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